While numerous diagnoses and physical assessments require the use of sophisticated equipment and extensive testing by specialists in clinics, a deeper understanding of biomarkers and their significance provides an opportunity to utilize this information in less obtrusive, less expensive, and less burdensome way. Recent technological advances, along with a better comprehension of metabolic, biochemical and physiological processes have enabled individuals to assume greater responsibility for their own wellness, health and physical fitness. Detection of such biomarkers may provide information that can assist individuals in assessing physiological status, and consequently making appropriate adjustments.
Numerous commercial tests are currently available to the general public, and such tests enable consumers to monitor their health in the privacy of their own homes, without the inconvenience or time-consuming activity of travelling to a healthcare or laboratory facility. Examples of such tests include the pregnancy test (biomarker detected is human chorionic gonadotropin (HCG), test media is urine), blood glucose test (biomarker detected is glucose metabolite, test media is blood), cholesterol test (biomarkers detected include HDL, LDL, and triglycerides, test media is blood), and prostate specific antigen (PSA) test (biomarker detected is PSA, test media is blood). The rising popularity of such tests supports the notion that consumers are becoming increasingly proactive about monitoring various aspects of their health, presumably in an effort to prevent illness and improve quality of life.
One particular segment of the population that is keenly attuned to their health and physical status comprises individuals that exercise on a regular basis and athletes. Their goals of maintaining good physical health are frequently coupled with, or closely tied to, maintaining good cardiovascular health.
Along with vascular aging and metabolic disorders, such as obesity, hypertension, and diabetic insulin resistance, prevalent promoters of cardiovascular disease are also on the rise. Although there is an inheritable basis to cardiovascular disease, poor diet and physical inactivity remain the primary drivers. Much of the latest biomedical research supports the need for a daily lifestyle comprising a cardioprotective diet as part of a solution.
Naturally produced nitric oxide is emerging as a critically important cardioprotective and vascular wellness factor. With age, arteries lose their elasticity and ability to make nitric oxide to prevent cardiovascular disease. Scientific evidence suggests that vascular aging may be delayed through the increased production of nitric oxide, thereby, enhancing cardiovascular function. Athletes have already taken advantage of these discoveries by increasing their consumption of leafy greens and beetroots, both of which are rich in nitrate, to elevate nitric oxide levels that increase endurance and performance.
A recent study (Apr. 15, 2013) conducted by researchers from Queen Mary University of London, and published in the American Heart Association Journal, Hypertension, provides further support for the importance of nitric oxide and of the blood pressure lowering effects on nitrate-rich vegetables. (Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductase and translational potential. Ghosh S M et al. Hypertension. 2013 May; 61(5):1091-102. Subjects who drank beetroot juice containing a natural source of inorganic nitrate show an average 10-point decrease in their blood pressure. Sustaining such levels may be critical in maintaining normal blood pressure. The lead author, Dr. Ahluwalia, reported to Medical Xpress: “our hope is that increasing one's intake of vegetables with a high dietary nitrate content, such as green leafy vegetables or beet root, might be a lifestyle approach that one could easily employ to improve cardiovascular health.”
A growing number of individuals, especially athletes, are interested in monitoring their nitric oxide status and modifying their whole food diets to optimize cardiovascular fitness. To determine whether an individual has consumed a sufficient quantity of nitric oxide-potent foods such as spinach, arugula, and beets, there is a need for a convenient method and device that is easy to use, and administer. Preferably such a method and device is simple, and inexpensive so that regular monitoring (even multiple times a day) is not burdensome either in the practice of the test or the cost of the test.
As mentioned previously, a number of devices for collecting and testing bodily fluids (i.e., saliva) for the presence of various metabolites exist in the art. In the context of providing a relatively quick and inexpensive sample collecting device and associated testing system, there exist several approaches for collecting a sample fluid, expressing the sample fluid in a test device and performing an assay of the sample. Examples of these types of testing systems include U.S. Pat. Nos. 5,965,453; 6,027,943; 4,895,808; 4,943,522; 6,267,722, 5,393,496, 7,763,433 and 7,507,374.
Prior art devices typically include a sample collector, a container for holding the sample collector and a testing apparatus. One type of sample collector typically includes an absorbent pad for absorbing the target fluid and a holder for holding the sample as the sample is being collected. The sample is then transferred to a sample container or test device by using one of a variety of known approaches including a mechanism for expressing the sample into a sample container (see U.S. Pat. No. 5,268,148) or dipping the sample collector into a test solution (see U.S. Pat. No. 4,895,808) or using a second filter or absorbent pad to transfer the fluid from the collector pad to an intermediate container or test device. Sample collectors may also include a sponge or chemical reagent disposed on a filter strip, which may indicate that an adequate sample is collected (see U.S. Pat. No. 5,393,496).
Strip tests with an absorption pad or chemical reagent test pad are often used in applications for home testing and rapid point of care testing. In some instances, the chemical reagent test pad also serves as the absorption pad.
A major limitation of using the above-mentioned tests for saliva is that since these tests typically incorporate at least one or more chemicals into the test pad/strip, they may not be directly- or safely-inserted into the mouth: in measuring metabolites found in the mouth, the chemical reagent test pad cannot be directly inserted into the mouth, because the chemical reagents can be harmful or toxic. Hence, in the case of saliva, a separated collection system is always necessary and is usually a separate device or apparatus or approach to transfer fluid to the test pad. An example of such a device is the NEO40® or NEOGENIS® test, which actually uses one's hand or finger to transfer the saliva to the test strip, i.e., spit on the finger and transfer spit to chemical test pad. (www.neogenis.com). Inevitably, such a design, where the saliva must first be obtained from the mouth and then transferred (i.e. by a finger) to the test pad, is not only awkward, but can also potentially contaminate results.
Other saliva tests involve a chemical reaction using a lateral flow membrane, that involves an encased test pad (which prevents contact with the mucosa of the mouth) and a wicking pad extension that is inserted into the mouth to collect saliva, which utilizes capillary action to migrate the saliva into the encased device containing the chemical test pad for the reaction to take place. Unfortunately, this is both an expensive (due to the encased device) and timely process, because of the amount of fluid which needs to be collected for the fluid to migrate into the chamber and for the fluid to make contact with the chemical reagents.
Therefore, currently available test strips are limited only to the chemical reaction, hence, the pad must be directly introduced into the test fluid outside of the mouth. Again, in the case of saliva fluid this creates a problem, since it would not be prudent to place the chemical reagent test pad directly into the mouth, as many of the dry test reagents comprise irritants, carcinogenic, or toxic chemicals that may be harmful, hence, the collection of saliva fluid is necessitates a separate device.
What is needed therefore are simple, easy to use devices that enable users to quickly, and accurately measure biomarkers of interest. In particular, what is needed are tests that can be used to detect biomarkers such as metabolites, chemicals, hormones, toxins, enzymes, immunoglobulins, proteins, and nucleic acids, in bodily fluids such as saliva, tears, sweat, urine, and blood. More particularly, a test that may be used directly in the oral cavity for measuring nitric oxide status is desired.